COVID-19 Scan for Aug 27, 2020

News brief

Review of COVID studies links increased death to hydroxychloroquine plus azithromycin

A systematic review and meta-analysis of studies involving COVID-19 patients treated with hydroxychloroquine found that the antimalaria drug alone was not associated with reduced mortality in hospitalized patients, but when combined with the antibiotic azithromycin it was linked with significantly increased mortality, European researchers reported yesterday in Clinical Microbiology and Infection.

The researchers looked at 29 studies published up until Jul 25, including 3 randomized controlled trials (RCTs) and 1 non-randomized trial. After excluding 11 studies with critical risk of bias, the meta-analysis included 11,932 patients treated with hydroxychloroquine, 8,081 treated with hydroxychloroquine and azithromycin, and 12,930 who received neither drug. The investigators compared mortality between patients treated with hydroxychloroquine and those treated with the standard of care, as well as death rates with hydroxychloroquine plus azithromycin.

The results of the meta-analysis showed that the relative risk (RR) of death for patients treated with hydroxychloroquine was 17% lower than for patients treated with standard of care (pooled RR, 0.83; 95% confidence interval, 0.65 to 1.06) for all studies and 9% higher for the RCTs (pooled RR, 1.09; 95% CI, 0.97 to 1.24). Neither of those results was considered statistically significant.

Treatment with hydroxychloroquine and azithromycin, however, was associated with a 27% increase in mortality compared with standard of care (pooled RR, 1.27; 95% CI, 1.04 to 1.54).

The authors of the study say the results confirm preliminary findings of several observational trials that showed the combination of hydroxychloroquine and azithromycin might increase the risk of life-threatening cardiovascular events.

"In conclusion, the meta-analysis clearly shows that hydroxychloroquine alone is not effective for the treatment of COVID-19 patients and that the combination of hydroxychloroquine and azithromycin increases the risk of mortality," they wrote.
Aug 26 Clin Microbiol Infect study

Comparison of COVID-19 antibody tests reveals wide range of performance

An evaluation of assays to detect antibodies against SARS-CoV-2, the virus that causes COVID-19, has found a wide range of performance, underscoring the need for rigorous test validation with standardized sample sets.

The study, published today in Nature Biotechnology, involved a comparison of 10 point-of-care lateral flow assays (LFAs) and two lab-based enzyme-linked immunosorbent assays (ELISAs) in 5-day intervals from symptom onset. Specificity was determined using blood samples donated before the pandemic.

Researchers studied 128 serum or plasma specimens from 79 patients who tested positive for COVID-19 at San Francisco hospitals. The percentage of specimens testing positive rose over time, peaking at 16 to 20 days and at more than 20 days. Four tests (Bioperfectus, Premier, Wondfo, and an in-house ELISA) had a positivity rate higher than 80% and specificity higher than 95%.

All assays' ability to detect immunoglobulin G was more consistent than that for immunoglobulin M, which affected overall test specificity (range, 84.3% to 100.0%). One LFA generated false-positive results in 30 samples.

The authors said that widely available, reliable antibody assays would produce more accurate estimates of COVID-19 prevalence and incidence. On Feb 4, the Department of Health and Human Services issued an emergency use authorization (EUA) for polymerase chain reaction and immunoassay diagnostic tests without formal Food and Drug Administration (FDA) approval. As a result, dozens of companies began selling lab-based and point-of-care tests without the backing of rigorous performance data.

The researchers called for validation using standard sample sets with known positive results from patients with different signs and symptoms at different time points, pre-pandemic blood samples, and control samples from people with other viral or inflammatory diseases.

"Coordinated efforts to ensure widespread availability of validated sample sets would facilitate data-driven decisions on the use of serology," they wrote. "The updated guidance released by the FDA in early May 2020 and the initiative recently launched by the FDA and the US National Cancer Institute/National Institutes of Health to systematize data generation for EUAs are substantive steps toward this goal."
Aug 27 Nat Biotechnol study

News Scan for Aug 27, 2020

News brief

Study: Feedback, education reduced antibiotic prescribing in telemedicine

Individualized prescribing feedback and education in a telemedicine practice significantly decreased antibiotic prescribing rates for upper respiratory infection (URI) and bronchitis compared with education alone, US researchers reported yesterday in the Journal of General Internal Medicine.

In a randomized controlled trial conducted at Doctor on Demand, a US telemedicine practice, from Jan 1 to Nov 30, 2018, a team lead by researchers from the Antibiotic Resistance Action Center at the George Washington Milken Institute of Public Health examined the effect of two antibiotic stewardship interventions on antibiotic prescribing for upper respiratory infection (URI), bronchitis, sinusitis, and pharyngitis—four conditions for which antibiotics are inappropriately prescribed or overprescribed. One group of clinicians at the practice (the control group) received education (treatment guideline presentation and an online course), and the intervention group received education plus individualized feedback via an online dashboard with monthly rates of personal and practice-wide prescribing rates.

The primary outcome of the trial was the antibiotic prescription rates for each of the four diagnostic categories.

In the pre-intervention period, the control and intervention groups had different baseline antibiotic prescribing rates for URI (18.4% vs 15.0%), bronchitis (46.8% vs 64%), sinusitis (84.1% vs 87.2%), and pharyngitis (81.3% vs 74.9%). Antibiotic prescriptions for all conditions decreased in the post-intervention period compared with those in the pre-intervention period. Compared with the control group, however, the reduction in antibiotic prescriptions for URI and bronchitis was greater in the group that received education plus individual feedback (interaction term ratio, 0.60; 95% confidence interval [CI], 0.47 to 0.77 for URI and 0.42; 95% CI, 0.32 to 0.55 for bronchitis). There was no significant difference between the two groups for sinusitis and pharyngitis.

The authors of the study note that in December 2018 Doctor on Demand expanded the intervention to provide feedback dashboards to all clinicians at the practice.

"These findings should be used to promote antibiotic stewardship across telemedicine and other ambulatory medical practices," the authors wrote. "Future studies should examine the long-term impact of education and feedback interventions, and maintenance of antibiotic prescription reductions."
Aug 26 J Gen Intern Med study

Ebola sickens 2 more in latest DRC outbreak; 106 cases, 46 deaths

Tests confirmed two more Ebola infections in the Democratic Republic of the Congo (DRC) outbreak in Equateur province, lifting the overall total to 106, the World Health Organization (WHO) African regional office said in a Twitter update today.

Two more deaths were reported, putting the outbreak's fatality count at 46.

The latest outbreak in the DRC began in early June, just as a large outbreak centered in North Kivu province was declared over. Genetic evidence suggests the two outbreaks aren't related, with the new one thought to be the result of a new zoonotic spillover where a similar, short-lived outbreak occurred in 2018.

Illnesses in the new outbreak, the DRC's 11th involving Ebola, are occurring across a wide area that ranges from remote areas that are hard for responders to reach to the provincial capital Mbandaka, which is located on a river and has travel connections to Kinshasa and neighboring countries.
Aug 27 WHO African regional office tweet

Zika virus infection may predispose to future severe dengue disease

Previous Zika virus infection can significantly enhance the risk of severe dengue disease, which could complicate the search for a Zika vaccine, according to a study published today in Science.

Researchers from the University of California at Berkeley studied data from two groups of Nicaraguan children who lived through epidemics with both mosquito-borne viruses: Zika in 2016 and dengue in 2019. They found that some antibodies to the Zika virus, which typically help protect against future Zika infections, may worsen future dengue infections, a phenomenon known as antibody-dependent enhancement.

Lead author Leah Katzelnick, PhD, said in a university press release that the findings raise important questions for Zika vaccine research: "Could a vaccine only targeted at Zika actually put people at increased risk of more severe dengue disease? And how can you design a Zika vaccine that only induces good antibodies that protect you against Zika, but doesn't induce these other, potentially enhancing antibodies that are harmful against disease?"

Dengue disease is caused by four related viruses that can each cause slightly different symptoms and illness severity. A person infected with one type of dengue virus is at higher risk for another, more severe illness when exposed to a second type of dengue virus. But if the person is infected with two types of dengue viruses, they typically are at least partially immune against severe dengue.

While the finding complicates development of safe and effective Zika vaccine, it could can help public health experts prepare for upcoming epidemics, senior author Eva Harris, PhD, said in the release. "So, for instance, if you have a dengue Type 2 epidemic after a big Zika outbreak, you know to prepare your hospitals to treat people who might be more likely to develop a more severe disease."
Aug 27 Science study and commentary
Aug 27 University of California at Berkeley press release

New Hampshire, Massachusetts report rare mosquito-borne illnesses

State officials in New Hampshire confirmed the state's third case of Jamestown Canyon virus (JCV) this week, as officials in Massachusetts confirmed its third human case of eastern equine encephalitis (EEE) virus infection this year.

Both viruses are spread by mosquitoes and relatively rare, but they can be deadly. In Massachusetts, the Department of Public Health (DPH) said the EEE case occurred in a man in his 90s who was exposed in Plymouth County.

"There have already been two other human cases identified this year. In 2019, there were 12 human cases of EEE in Massachusetts with 6 deaths," the DPH said.

In New Hampshire, an adult from Dumbarton was hospitalized with a fever and headache and diagnosed as having JCV.

"This is the third detection of Jamestown Canyon Virus infection in our State this year, and the risk for Jamestown Canyon Virus and other mosquito-transmitted viral infections will only increase until there is a mosquito-killing hard frost in the fall," said Benjamin Chan, MD, MPH, state epidemiologist.
Aug 19 Massachusetts DPH notice
Aug 21 New Hampshire DHHS notice

Avian flu outbreaks strike birds in Australia and Russia

Animal health officials in Australia reported new avian flu outbreaks in commercial birds involving two separate strains, low-athogenic H7N6 and highly pathogenic H7N7, according to notifications from the World Organization for Animal Health (OIE).

The H7N6 outbreak, the country's first involving the strain since 2013, began on Aug 18 at a commercial emu farm in Kerang, Victoria, killing 100 of 8,753 susceptible birds. Clinical signs were seen only in chicks. The source of the virus isn't known but could related to contact with wild birds, according to the report. Culling and disinfection are planned for the site.

Regarding H7N7, the latest outbreak appears to be linked to recent detections at layer farms in Victoria state. The new outbreak began on Aug 23 at a farm in Lethbridge, Victoria, killing 15 of 36,878 susceptible birds. The rest were culled, and the facility is being disinfected.

Australia also recently reported outbreaks from a third strain, low pathogenic H5N2, which turned up on turkey farms, also in Victoria state.
Aug 26 OIE report on H7N6 in Australia
Aug 25 OIE report on H7N7 in Australia

Elsewhere, Russia recently reported three highly pathogenic H5 avian flu outbreaks in village and backyard poultry in Omsk Oblast, located in southwest Siberia, according to an OIE report. The events began on Aug 11, killing 266 of 543 birds. Culling is in progress. So far, the source of the virus isn't known.

Earlier this month, Russia reported two outbreaks involving H5N8 in backyard and village poultry in Chelyabinsk Oblast, located in the Ural Mountains near the border with Europe and Asia.
Aug 25 OIE report on H5 in Russia